Effects of lamotrigine on mood in older adults with epilepsy and co-morbid depressive symptoms: an open-label, multicentre, prospective study.
ABSTRACT Both epilepsy and depressive symptoms are more prevalent in older individuals than in any other age group. Furthermore, depressive symptoms are among the most common interictal psychiatric co-morbid disorders in people with epilepsy. For these reasons, pharmacological treatment of epilepsy that might also confer antidepressant effects may be particularly beneficial in older patients. In this respect, lamotrigine is of considerable interest amongst antiepileptic drugs (AEDs) because it has proven thymoleptic activity.
These analyses, conducted on a data set drawn from a previously reported, open-label, multicentre, prospective study, examined the effect of lamotrigine on mood in adults aged>or=50 years with epilepsy and co-morbid depressive symptoms. All subjects were receiving background AED therapy at baseline.
Of the 158 subjects enrolled in the initial study, 40 adults (24 women, 16 men) met the age criterion for these analyses. The study consisted of a screening/baseline phase and four treatment phases over 36 weeks: lamotrigine escalation phase (7 weeks); lamotrigine maintenance or adjunctive therapy phase (12 weeks); concomitant AED withdrawal phase (5 weeks); and lamotrigine monotherapy phase (12 weeks). Psychometric evaluation of mood utilized the Beck Depression Inventory (BDI-II), Center for Epidemiological Studies Depression Scale (CES-D), the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E) and the Profile of Mood States (POMS). Scores at the end of the adjunctive and monotherapy phases were compared with baseline scores. Lower scores on these scales indicate less depressive symptomatology.
Mean baseline scores for the BDI-II, CES-D, NDDI-E and POMS were 15.8, 24.3, 13.8 and 57.7, respectively. Change scores were statistically significant (p<0.01) compared with baseline at the end of the adjunctive and monotherapy phases for all four psychometric measures of mood, with the exceptions of BDI-II and NDDI-E at the end of the adjunctive phase.
The older adults in these analyses presented with low to moderate levels of depressive symptoms. Addition of lamotrigine to background AED therapy demonstrated antidepressant activity similar to that for the whole sample in the initial study. Given that the onset and prevalence of epilepsy are higher in older adults than in any other age group, pharmacological treatment for epilepsy in older patients that might also confer antidepressant therapy may be particularly beneficial.
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ABSTRACT: Despite collection of patient reported outcome (PRO) data in clinical trials of antiepileptic drugs (AEDs), PRO results are not being routinely reported on European Medicines Agency (EMA) and Food and Drug Administration (FDA) product labels. This review aimed to evaluate epilepsy-specific PRO instruments against FDA regulatory standards for supporting label claims. Structured literature searches were conducted in Embase and Medline databases to identify epilepsy-specific PRO instruments. Only instruments that could potentially be impacted by pharmacological treatment, were completed by adults and had evidence of some validation work were selected for review. A total of 26 PROs were reviewed based on criteria developed from the FDA regulatory standards. The ability to meet these criteria was classified as either full or partial, whereby partial reflected some evidence but not enough to comprehensively address the FDA regulatory standards. Most instruments provided partial evidence of content validity. Input from clinicians and literature was common although few involved patients in both item generation and cognitive debriefing. Construct validity was predominantly compromised by no evidence of a-priori hypotheses of expected relationships. Evidence for test-retest reliability and internal consistency was available for most PROs although few included complete results regarding all subscales and some failed to reach recommended thresholds. The ability to detect change and minimally important difference/responder definition were not investigated in most instruments and no PROs had published evidence of a conceptual framework. The study concludes that none of the 26 have the full evidence required by the FDA to support a label claim, and all require further research to support their use as an endpoint. The Subjective Handicap of Epilepsy (SHE) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) have the fewest gaps that would need to be addressed through additional research prior to any FDA regulatory submission, although the NDDI-E was designed as a screening tool and is therefore unlikely to be suitable as an instrument for capturing change in a clinical trial and the SHE lacks the conceptual focus on signs and symptoms favoured by the FDA.Health and Quality of Life Outcomes 03/2013; 11(1):38. DOI:10.1186/1477-7525-11-38 · 2.10 Impact Factor
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ABSTRACT: OBJECTIVES: To examine the association between antiepileptic drug (AED) receipt and suicide-related behavior (SRB) in older veterans. DESIGN: Retrospective database analysis. SETTING: Veterans Health Administration (VHA) inpatient and outpatient care. PARTICIPANTS: Veterans aged 65 and older in 2004 to 2006. MEASUREMENTS: SRB was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes, and new AED monotherapy was identified using the VHA product variable in pharmacy data. Comorbid conditions and medications were also identified as potential confounders using previously validated algorithms. Cox proportional hazards models controlling for the propensity to receive AEDs examined the association between any AED exposure, specific AEDs, and time to SRB. RESULTS: Within the eligible sample of 2.15 million individuals, 332 cases of SRB were found. Overall, 98% of participants were male, and 67% were non-Hispanic white. Affective disorders and severe psychiatric conditions were strongly associated with SRB and were included in the propensity score. AED exposure displayed a significant association with SRB (odds ratio = 4.10, 95% confidence interval (CI) = 3.85-6.63) after adjusting for propensity to receive AEDs. Stratified analyses found similar results for those with (hazard ratio (HR) = 4.00, 95% CI = 2.9-5.5) and without (HR = 4.57, 95% CI = 1.15-18.20) mental health comorbidities. Gabapentin, phenytoin, lamotrigine, levetiracetam, topiramate, and valproate were significantly associated with SRB. CONCLUSION: Exposure to five common AEDs was associated with SRB in older VHA beneficiaries. Given the strong associations between psychiatric comorbidity and SRB, clinicians treating elderly adults should weigh this potential adverse effect into their consideration for treatment of those receiving AEDs. Particular attention should be given to depression and suicidality screening in people prescribed AEDs.Journal of the American Geriatrics Society 10/2012; 60(11). DOI:10.1111/j.1532-5415.2012.04207.x · 4.22 Impact Factor
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ABSTRACT: Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.The Tohoku Journal of Experimental Medicine 02/2014; 232(2):123-8. DOI:10.1620/tjem.232.123 · 1.28 Impact Factor